Ginsenoside Rg2 Ameliorates Alzheimer's Disease by Alleviating Neuroinflammation in APP/PS1 Mice.

Introduction: Ginsenoside Rg2 (GRg2), a naturally occurring triterpenoid derived from ginseng rhizomes, exhibits neuroprotective properties. Neuroinflammation is recognized as one of the key pathogenic mechanisms underlying Alzheimer's disease (AD). This research aims to investigate the beneficial effects of GRg2 on AD and explore its potential mechanisms.

Methods: In APP/PS1 mice, cognitive and behavioral assessments were first performed. Subsequently, brain tissue analyses were performed using immunohistochemical analysis and Western blot. A combined analysis of the gut microbiome and metabolomics was conducted to explore potential mechanisms. Finally, key findings were further validated through immunofluorescence and enzymelinked immunosorbent assay.

Results: GRg2 enhanced learning, memory, and cognitive functions. And inhibits the deposition of β- amyloid and phosphorylated tau. GRg2 effectively inhibits the production of Bacteroides and Helicobacter. In addition, it reduced the levels of pyruvaldehyde and trimethylamine N-oxide, metabolites closely related to neuroinflammation. GRg2 effectively inhibited the activation of astrocytes and microglia in the brains of APP/PS1 mice, and also reduced the expression of neuroinflammatory mediators IL-6, IL-1β, and TNF-α.

Discussions: The findings of this study substantiate the neuroprotective efficacy of GRg2, providing a novel therapeutic strategy and theoretical foundation for natural product-based interventions against AD.

Conclusion: GRg2 improves cognitive function and mitigates AD pathology, which is at least partially attributed to its regulation of gut microbiota and metabolites, as well as its anti-neuroinflammatory effects.